A Severe, Refractory Case of Mucous Membrane Pemphigoid After Treatment With Pembrolizumab: Brief Communication
Pembrolizumab is a humanized antibody that targets the programmed death-1 receptor expressed in T cells with high selectivity. This therapeutic is of great importance in cancer immunotherapy yet managing the potential immune-related adverse events remains a concern. Here, we report a rare case of mucous membrane pemphigoid in the oral mucosa, upper respiratory tract, and conjunctiva of a patient with ovarian adenocarcinoma without cutaneous manifestation, which persisted even after pembrolizumab discontinuation. A brief review of pembrolizumab-related bullous pemphigoid cases is presented and possible mechanisms underlying...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Immunogenomic Analysis of Exceptional Responder to ALT-803 (IL-15 Analogue) in BCG Unresponsive Nonmuscle Invasive Bladder Cancer: A Case Series and Review of the Literature
The clinical validity and utility of complex biomarkers have not been extensively studied in bladder cancer. Three patients with nonmuscle invasive bladder cancer [1 patient with an exceptional response; complete response (CR) for 30 months] who failed intravesical BCG were evaluated using an NYS CLEP approved assay, Immune Report Card, which measures programmed death-ligand 1 expression, CD8+ T-cell infiltration pattern, mutational burden, and gene expression of 51 immune-related transcripts using RNA-Seq. Patients were tested before being treated under our expanded access protocol for intravesical BCG with ALT-803. Subje...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Superimposed Clostridium difficile Infection During Checkpoint Inhibitor Immunotherapy-induced Colitis
This report described the course of the 2 medical conditions in these patients. On the basis of our experiences, CDI may occur as a superimposed infection during ICI-induced colitis. Although ICI-induced colitis may be a risk factor for CDI, the observed association may be fortuitous. Future study will be needed to characterize the association between CDI and ICI-induced colitis. Clinicians should be mindful of possible co-occurrence of both conditions to promptly and adequately institute effective interventions. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Nivolumab and Ipilimumab-induced Acute Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report
Immunotherapies such as the cytotoxic T-lymphocyte–associated protein 4 inhibitor ipilimumab and the programmed cell death protein 1 inhibitor nivolumab have become ubiquitous in cancer treatment. Recently, the FDA approved nivolumab with or without ipilimumab for the treatment of refractory small cell lung cancer. Immunotherapies increase the immune response to cancer cells by interfering with inhibitory molecular pathways that prevent tumor cell killing, thus augmenting tumor cell death without many of the cytotoxic side effects associated with chemotherapy. However, this augmented immune response may result in unwante...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Linear IgA Disease of the Gingiva Following Nivolumab Therapy
We report the first case of gingival linear immunoglobulin A disease related to treatment with an antiprogrammed cell death protein 1 antibody. A 73-year-old male with advanced non–small cell lung cancer achieved a durable response to nivolumab monotherapy. After 1 year of treatment, he developed gingival swelling and pain. Biopsy revealed linear immunoglobulin A disease of the gingiva which was effectively treated with systemic steroids. Ongoing vigilance for immune-mediated toxicity is paramount during and after treatment with immune checkpoint inhibitors. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell–specific Stimulation and Therapeutic Monoclonal Antibodies
This study expands on earlier reports on the therapeutic potential of distinctive tumor antigen–targeting mAbs and facilitates the understanding of the mechanism and potential of ADCC by γδ T-cell subsets. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Checkpoint Blockade in Combination With Doxorubicin Augments Tumor Cell Apoptosis in Osteosarcoma
The aim of this study was to provide a basis for the theory that the combination of conventional chemotherapy and immunotherapy would be an effective treatment for osteosarcoma. Here, the expression of programmed death ligand 1 (PD-L1) in 26 clinical osteosarcoma tissue samples collected before and after chemotherapy was analyzed. The effects of osteosarcoma cells treated with doxorubicin, a conventional chemotherapeutic agent, on the proliferation and apoptosis of CD8+ T lymphocytes were investigated in vitro. Thereafter, the effectiveness of doxorubicin combined with an anti-PD-L1 antibody as an osteosarcoma therapy was ...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Autoimmune Bell’s Palsy Following Immunotherapy For Metastatic Melanoma: A Report of 2 Cases
We describe 2 cases of autoimmune Bell’s palsy following the administration of combination ICT using ipilimumab and nivolumab in 2 patients with metastatic melanoma. The use of a steroid taper in addition to the cessation of combination immunotherapy resulted in resolution of symptoms for both patients. In the first case, the patient was subsequently started on nivolumab monotherapy but developed autoimmune polyneuropathy, and immunotherapy was discontinued indefinitely. In the second case, the initiation of nivolumab monotherapy following resolution of symptoms resulted in an inadequate antitumoral response. Subsequent ...
Source: Journal of Immunotherapy - September 7, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research
Combination Nivolumab/Ipilimumab Immunotherapy For Melanoma With Subsequent Unexpected Cardiac Arrest: A Case Report and Review of Literature
We present a case of extensively metastatic oral mucosal melanoma that responded successfully to combined immune checkpoint blockade with ipilimumab and nivolumab but developed multiple immune-related adverse events, including myocarditis, a rare event associated with immunotherapy of elderly melanoma patients. Though the acute myocarditis was managed successfully, the patient succumbed to sudden cardiac death. This case highlights the fact, that autoimmune carditis must be considered when working up the sudden onset of shortness of breath in patients on immune checkpoint blockade. After controlling the acute myocarditis w...
Source: Journal of Immunotherapy - September 7, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research
Myasthenia Gravis Induced by Immune Checkpoint Inhibitors
We report a case of our experience and review the current literature of MG exacerbated or occurring during immunotherapy to describe characteristics of this AE, warn the oncologist about this toxicity, and summarize the treatments conducted. Thirty-four cases of MG were reported, mostly with anti-programmed cell death protein 1 checkpoint inhibitor, and with melanoma. Onset was quick after the first or second infusion. Treatment comprised corticosteroids, prostigmine, and more or less plasmapheresis or immunoglobulins. Prognosis is poor, as 13 patients died after MG. MG is a rare immune-related AE that must be rapidly evok...
Source: Journal of Immunotherapy - September 7, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research
PD-1 Expression and Function of T-Cell Subsets in TILs From Human Lung Cancer
On the basis of the autologous tumor-infiltrating lymphocytes (TILs) or genetically modified TILs for adoptive cell therapy have received more attention. Programmed cell death protein 1 (PD-1) expression on the T cells exert complex response during the tumor immune response. But the composition and function of PD-1+T-cell subsets in TILs from human lung cancer still limited. In blood and TILs from human lung cancer patients, we confirmed that PD-1 is expressed in higher levels in CD4+T-cell subsets than in CD8+T-cell subsets. To further analyze the function of PD-1+T cells in TILs, we observed the cytokine production in di...
Source: Journal of Immunotherapy - September 7, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Anti-αFR CAR-engineered NK-92 Cells Display Potent Cytotoxicity Against αFR-positive Ovarian Cancer
Folate receptor alpha (αFR) is overexpressed in 90% of ovarian cancers, one of the most lethal gynecologic cancers. Recent studies have suggested that natural killer (NK) cells may be better chimeric antigen receptor (CAR) drivers because of their favorable innate characteristics, such as directly recognizing and killing tumor cells. However, the therapeutic effects of CAR-engineered NK cells targeting αFR in ovarian cancer have not been reported. In this research, 3 generations of anti-αFR CAR were constructed, namely αFR-ζ (first generation), αFR-28ζ (second generation), and αFR-28BBζ (third generation), and wer...
Source: Journal of Immunotherapy - September 7, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
LAG3 in Solid Tumors as a Potential Novel Immunotherapy Target
We performed a prospective immunohistochemical analysis of lymphocyte activation gene 3 (LAG3) for 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Most patients (428/430, 99.5%) were evaluable for LAG3 expression by immunohistochemistry. In total, 18.5% (79/428) of the evaluated cancers expressed LAG3, including pancreatic cancer (33.3%, 2/6), gastric cancer (24.7%, 21/85), colorectal cancer (23.6%, 48/203), melanoma (12.5%, 1/8), genitourinary cancer (9.5%, 4/46), biliary tract cancer (6.3%, 1/16), and sarcoma (5.4%, 2/37), but not miscellaneous (0....
Source: Journal of Immunotherapy - September 7, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Metastatic Mixed Adenoneuroendocrine Carcinoma of the Colon with Response to Immunotherapy with Pembrolizumab: A Case Report
We present the case of a 51-year-old female patient with histopathologically confirmed diagnosis of a MANEC of the descending colon. At presentation, the tumor had already spread to the liver causing extensive hepatic metastases. Immunohistochemical examination showed 5%–10% of tumor cells to express the programmed cell death receptor ligand 1 and FoundationOne testing revealed a high mutational tumor burden with 149 Muts/Mb. The patient responded very well clinically and radiologically to anti-programmed death 1 receptor monoclonal antibody pembrolizumab therapy after having undergone 3 previous systemic treatment regim...
Source: Journal of Immunotherapy - August 9, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research
PD-L1 Expression in De Novo Metastatic Castration-sensitive Prostate Cancer
De novo metastatic castration-sensitive prostate cancer (mCSPC) is small subgroup of prostate cancer associated with poor prognosis. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) in tumor cells of de novo mCSPC patients. Patients referred to our institution from January 2007 to October 2017 with de novo mCSPC and available diagnostic tissue were included. We tested the PD-L1 pharmaDx qualitative immunohistochemical assay, a monoclonal rabbit anti-PD-L1, clone 28-8 intended for use in the detection of PD-L1 protein in formalin-fixed paraffin-embedded. Kaplan-Meier method was used to ...
Source: Journal of Immunotherapy - August 9, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research
